We have shown in dogs that somatostatin regulates the rate at which ingested nutrients enter the circulation, but the ability to study D-cell function in man has been limited technical problems in the RIA. We are now developing a practical radioimmunoassay for somatostatin in human plasma as was done earlier in dogs. If successful, we intend to study human D-cell function, in particular the somatostatin response to meals in normal subjects, obese nondiabetic subjects, obese and nonobese adult onset diabetics and juvenile onset diabetics There are reasons to wonder if some forms of obesity may not result from an inadequate meal-induced rise in somatostatin, causing more rapid entry of ingested nutrients into the circulation, with compensatory hyperinsulinemia being necessary to prevent high levels of the ingested glucose, amino acids, etc. The fact that the gastrointestinal tract is empty for a greater fraction of each day may itself increase appetite and food intake. We plan to correlate gastric emptying and/or other rate-limiting gastrointestinal functions with somatostatin response to meals, and where somatostatin is deficient, to determine if replacement infusions will correct and observed GI hyperfunction. We will also study juvenile diabetics, expecting basal hypersomatostatinemia with a reduced postprandial rise in somatostatin, as we observed in severe alloxan diabetic dogs; this may contribute to the gastroparesis and other of their gastrointestinal abnormalities. D-cell function will also be examined in a variety of other conditions including "dumping syndrome", other states characterized by rapid transit of nutrients, pernicious anemia and peptic ulcer, etc. The significance and importance of this work derives from the probability that somatostatin is the key hormone in regulating the movement of nutrients from the external to the internal environment, and the possibility that defects in such control may be a factor in human illness.